Selective Stimulation of Duplicated Atlantic Salmon MHC Pathway Genes by Interferon-Gamma

Induction of cellular immune responses rely on Major histocompatibility complex (MHC) molecules presenting pathogenic peptides to T cells. Peptide processing, transport, loading and editing is a constitutive process in most cell types, but is accelerated upon infection. Recently, an unexpected complexity in the number of functional genes involved in MHC class I peptide cleavage, peptide transport, peptide loading and editing was found in teleosts, originating from the second and third whole genome duplication events. Salmonids have expanded upon this with functional duplicates also from a fourth unique salmonid whole genome duplication. However, little is known about how individual gene duplicates respond in the context of stimulation. Here we set out to investigate how interferon gamma (IFNg) regulates the transcription of immune genes in Atlantic salmon with particular focus on gene duplicates and MHC pathways. We identified a range of response patterns in Atlantic salmon gene duplicates, with upregulation of all duplicates for some genes, like interferon regulatory factor 1 (IRF1) and interferon induced protein 44-like (IFI44.L), but only induction of one or a few duplicates of other genes, such as TAPBP and ERAP2. A master regulator turned out to be the IRF1 and not the enhanceosome as seen in mammals. If IRF1 also collaborates with CIITA and possibly NLRC5 in regulating IFNg induction of MHCI and MHCII expression in Atlantic salmon, as in zebrafish, remains to be established. Altogether, our results show the importance of deciphering between gene duplicates, as they often respond very differently to stimulation and may have different biological functions.